The prior art generally is discussed in some detail in my U.S. Pat. Nos. 5,360,605 and 5,370,869 along with specific discussions of the most relevant prior art references. It is sufficient to summarize the state of the art as follows: After at least three decades of clear recognition of the serious and immediate need for methods to remove pathogenic virus, and other microbes, from blood, blood products, fractions and derivatives, and other biological liquids, the serious and immediate need remains untilled. After nearly two decades of near panic search for a solution to the aforementioned problem following the catastrophic spreading of AIDS via the blood banking system, the problem remains unsolved in need of an immediate solution on an increasingly urgent basis.
For the three decades referred to, indeed, for almost a century, iodine has been known to all workers to be an effective contact biocide; indeed, iodine, in its various forms, is probably the most widely used and universally known biocidal material in medical history. A history of the relevant uses of iodine and the sources of iodine and iodine compounds is given in my aforesaid United States Patents, the disclosure of which is incorporated herein by reference.
Rubinstein, U.S. Pat. No. 5,185,371, discusses the long standing opposition to the use of iodine in blood which characterized, and still characterizes the general skill of the art. Referring to iodine and other oxidizers, Rubinstein summarizes the prior art in the following terms: "None of these disinfectants have been applied to disinfecting blood products or tissue products. Such compositions in contact with blood and tissue products would cause one to expect resultant damage to the cells and tissue." U.S. Pat. No. 5,185,371, col. 2, lines 43-48. Rubinstein asserts that the well-known disadvantages of iodine as a biocide can be overcome by using iodine in isotonic solutions. Unfortunately, however, even Rubinstein's proposed use of isotonic iodine solutions alone has not solved the long standing and urgent health care problem of infected blood and blood products.
At my direction, a comprehensive survey of the literature on the subject of iodine as a biocide was conducted. Following an analysis of the literature, I concluded, as had most other workers, that there was little hope that iodine or iodine compounds could be used effectively in the processing of blood. Not withstanding the serious problems I set about to develop, if possible, methods for treating blood and blood constituents, plasma in particular, with iodine or iodine compounds to eliminate pathogens, e.g. HIV and hepatitis virus, without altering the biological material to be treated. Many methods have been developed. Much was learned about the use of iodine, in several forms, in biological materials. Several methods that initially appeared attractive, especially considering the overwhelming shadow of doubt that overlies the entire subject, were developed. Very importantly for current products and processes and future research, I have also developed general criteria that relate to the killing of virus in biological fluids, specifically in blood fractions and solutions containing blood constituents. While, it has not always been possible to quantify with exactitude the effect of the various parameters involved certain critical parameters have been discovered and defined.
There is some literature that makes reference to the effect of pH on the virucidal effectiveness of iodine. The problem, however, was defined only in broad terms that were not helpful. Such little definition of the problems as existed were unaccompanied by suggestion as to solving the problems involved in using iodine. It has been established that the virucidal effectiveness of iodine increases as pH decreases below pH 7.0, and, significantly increases as the pH decreases below about 6.0. However, the combination of low pH and iodine alters many blood proteins, certain of the clotting factors in particular, rendering such processes unusable in most situations. This is especially true if iodine is added as Lugol's solution. The addition of comparable amounts of iodine as povidone iodine decreases the rate and/or amount of protein alteration, but also decreases the virucidal effectiveness of iodine on a short contact-time basis. Several approaches were taken to provide iodine-based processes that would reliably and effectively kill pathogenic virus, but no entirely satisfactory iodine-based process has hitherto been found. The term "pathogenic virus" is used here in its ordinarily understood sense to refer to a virus that is capable of causing disease in man or animal.
Many methods and materials exist for introducing iodine into blood fractions and products. Some of these methods and materials show great promise both in providing a high level of virucidal action and in acceptable protein function losses; nevertheless, results are not always consistent and variations in protein function are often great and inexplicable. It has, therefore, become apparent that the use of special methods and materials for introducing iodine into blood and blood products will not, alone, result in a reliable, virucidally effective method for treating such products with acceptable protein function loss.
In general, my work has corroborated the implications of the prior art, namely, that methods based on the use of iodine in blood and blood products are not, alone, satisfactory methods of preparing safe blood products. Iodine could be added by several methods using several iodine source-compounds at such a level as to result in a complete kill of most virus; however, excessive losses of important protein functions, the clotting functions, for example, and degradation of the product occurred. I also explored in considerable depth the use of what I call the "capture" concept, namely the removal of iodine from the blood product after addition of the iodine for biocidal purposes. I determined that there was, in some instances, an advantage in removing the biocidal iodine within a relatively short period of time following addition; however, no entirely satisfactory removal system has heretofore been developed and results were not definitive or consistent. For example, it was known that povidone would "capture" iodine from solution and several forms of povidone were tested as capture materials. Such capture materials were not satisfactory, however, because of incomplete capture and re-iodination from the capture material. Re-iodination occurred when the capture material had absorbed iodine from the liquid being treated. This results in the release of iodine back into subsequent aliquots of such material as it passes through the capture material. Starch is, in theory, an effective capture material, but starch beds or columns tended to channel and/or clog.
The present invention is based on the discovery that a distinctive type of material does not channel or clog and substantially irreversibly captures iodine from biological liquids such as blood, blood fractions and derivatives.
Having experienced years of alternating hope and discouragement and many disappointments in research seeking to use the generally recognized biocidal effectiveness of iodine to treat blood and blood derivatives and products, I have, I believe, discovered one solution to many of the problems predicted by earlier and contemporaneous workers, and which my earlier work established.